Two types of influenza vaccines are currently licensed in the US, trivalent inactivated vaccine (TIV), administered by intramuscular injection, and LAIV, administered by nasal spray. Both vaccines are safe and effective in their approved age groups. Neutralizing antibody in the serum has been found to be a correlate of protection for TIV, but the immune correlates of protection for LAIV are not known. Defining the origin and nature of transcriptional responses to LAIV in URT in infected and bystander epithelial and lymphocyte cells in healthy adults will be a highly informative first step in a systems approach toward understanding the molecular basis of viral replication restriction and the regulation of the local mucosal immune responses following LAIV administration.